Novel multifunctional hydroxy compounds

ABSTRACT

N-alkylated derivatives of 2-amino-2-hydrocarbylthiomethyl-1,3propanediols useful as flotation agents, rubber modifiers, and chelating agents in the separation of metals are produced by reacting 2-amino-2-hydrocarbylthiomethyl-1,3-propanediols with organic halides. Thiols can be produced by reacting arylmethylated or alkarylmethylated derivatives of the above compounds with an alkali metal in the presence of ammonia.

United States Patent [191 Bresson et al.

[4 1 Jan. 29, 1974 NOVEL MULTIFUNCTIONAL HYDROXY COMPOUNDS [75] Inventors: Clarence R. Bresson; Raymond L.

Cobb, both of Bartlesville, Okla.

[73] Assignee: Phillips Petroleum Company,

Bartlesville, Okla,

[22] Filed: Apr. 22, 1971 {21] Appl. No.: 136,603

Related US. Application Data [62] Division of Ser. No. 749,990, Aug. 5, 1968, Pat. No.

3,609,189, which is a division of Ser. No. 492,892,

Oct. 4, 1965, Pat. No. 3,414,617.

[52] U.S.- Cl 260/514 J, 260/514 G, 260/516,

{51 i111. cl, If. f ..C07c 149124, C07c 149/2'6, C070 149/42 [58] Field ofSearch ..260/5l4.l, 534 M,534 S, 260/516 C,5l6 A [56] References Cited UNITED STATES PATENTS 3,414,617 12/1968 Bresson ..260/57OS OTHER PUBLICATIONS Blatt, Organic Synthesis, Coll. Vol II, 397 (1943).

Satchell, Quarterly Reviews, 1963, Volume XVII pp. 185-187.

Primary Examinerl ,orraine A. Weinberger Assistant ExaminerRobert Gerstl Attorney, Agent, or FirmYoung & Quigg [57] ABSTRACT 13 Claims, No Drawings NOVEL MULTIFUNCTIONAL HYDROXY COMPOUNDS This is a divisional of application Ser. No. 749,990 filed Aug. 5, 1968 issued as US. Pat. No. 3,609,189, on Sept, 28, 1971, which is a division of application Ser. No. 492,892 filed Oct. 4, 1965 issued as US. Pat. No. 3,414,617, on Dec. 3, 1968.

In one aspect this invention relates to novel hydrocarbylthiomethyl and mercaptomethylsubstituted propanediols. In another aspect this invention relates to N-alkylated derivatives of 2-amino-2- hydrocarbylthiomethyl-l,3-propanediols. In still another aspect, this invention relates to a method for preparing such novel compounds.

In accordance with this invention, an N-alkylated derivative of a 2-amino-2-hydrocarbylthiomethyl-1,3- propanediol having the formula CRzOH (I) is produced by the reaction of a 2-amino-2- hydrocarbylthiomethyl-l ,3-propanediol having the formula CR OH n with an organic halide having the formula R"X whereby R replaces one of the hydrogens on the amino group with the liberation of HX.

With reference to the above formulae, R is at least one member selected from the group consisting of hydrogen and alkyl containing 1-3 carbon atoms; R is a monovalent hydrocarbyl radical selected from the group consisting of alkyl, cycloalkyl, aryl, and combinations thereof such as alkaryl, aralkyl, and the like, said monovalent hydrocarbyl radical containing 1-12 carbon atoms; R" is a member selected from the group consisting of unsubstituted and substituted alkyl, cycloalkyl, and aralkyl radicals, and combinations thereof such as alkylcycloalkyl, alkylaralkyl, and the like, containing 1-12 carbon atoms, the substituent in the substituted radicals being a monovalent radical such as hydroxy, hydrocarbyloxy, hydrocarbylthio, carboxy, carbamoyl, and the like; and X is a halogen selected from the group consisting of chlorine, bromine, and iodine, preferably chlorine or bromine; and wherein the number of carbon atoms in Formula I is within the range of 6-36.

Examples of novel products made according to the process described hereinabove are as follows:

2-methylamino-2-methylthiomethyl-1 ,3-propanedio] 2-ethylamino-2-[ l-(isopropylthio)butyl]- l ,3-

propanediol 2-isopropylamino-2-l l-( ethylthio )ethyl l ,3-

propanediol 2-tert-butylamino-2-[ 1-(sec-butyIthio)-1-methylpropy]]- l ,3-propanediol 2-hexylamino-2-tert-butylthiomethyl-1 ,B-butanediol 3-( 1 ,Z-diethylpentylamino)-3-hexylthiomethyl-2,4-

hexanediol 2-dodecylamino-2-( 3-methyloctyl)thiomethyl- 1 ,3

hexanediol 5-dodecylamino-5-[ l-(dodecylthio )propyl]-4,6-

nonanediol 2-cyclohexylamino-2-decylthiomethyl- 1 ,3-

propanediol 2-( 2-methylcyclopentylamino )-2- cyclohexylthiomethyl-4-methyl- 1 ,3-pentanediol 2-( 2-cyclohexylethylamino)-2-phenylthiomethyll ,3-propanediol 2-(2-phenylethylamino)-2-p-tolylthiomethy1- 1 ,3- V

propanediol 2-(4-methylbenzylamino)-2-[ l-(propylthio)-2- methylpropyl1- 1 ,3-propanediol 5-(3-l1ydroxypropylamino)-5-[ l-(dodecylthio)- propyl]-4,6-nonanediol 2-(4-ethoxybutylamino )-2-methylthiomethyl-3- methyl-1 ,3-butanediol 2-( 3-methylthiopropylamino )-2-propylthiomethyl- 1 ,3-propanediol 2-( 3-carboxycylopentylamino)-2-butylthiomethyl 1 ,3-propanediol 2-( 3-carbamoylpropylamino )-2-phenylthiomethyl- 1 ,3-propanediol 2-methylamino-2-benzylthiomethyl-1 ,3-butanediol Examples of compounds of Formula II suitable for reacting with an organic halide are the following:

2-amino-2-methylthiomethyl-1 ,3-propanediol 2-amino-2-[ l-(ethylthio)ethyl]-1,3-propanediol 2-amino-2-[ 1-(isopropy1thio)butyl]-1 ,3-propanediol 2-amino-2-[ 1-(sec-butylthio)- 1-methylpropyl]-1 ,3-

propanediol 2-amino-2-tert-butylthiomethyll ,3-butanediol 3-amino-3-hexylthiomethyl-2,4-hexanediol 2-amino-2-( 3-methyloctyl)thiomethyll ,3-

hexanediol 2-amino-Z-decylthiomethyl-1 ,3-propanediol 2-amino-2-cyclohexylthiomethyl-4-methyl-1 ,3-

pentanediol 2-amino-2-phenylthiomethyl-1 ,S-propanediol 2-amino-2-p-tolylthiomethyl-1 ,3-propanediol 2-amino-2-[ 1-(propylthio)-2-methylpropyl]-1 ,3-

propanediol 5-amino-5-[ 1-(dodecylthio)propyl]4,6-nonanediol 2-amino-2-methylthiomethyl-3-methyl- 1 ,3-

butanediol 2'amino-2-benzylthiomethyl-l ,3-butanediol Examples of organic halide compounds suitable in the process of this invention are the following:

bromomethane iodoethane 2-chloropropane 2-bromo-2-methylpropane l-chlorohexane 3-bromo-4-ethylheptane l-chlorododecane chlorocyclohexane 1-bromo-2-methylcyclopentane 1 -iodo-2-cyclohexylethane l-chloro-2-phenylethane a-bromo-p-xylene 3-bromopropanol l -chloro-4-ethoxybutane 1-bromo-3-methylthiopropane l-chloro-3-carboxycyclopentane 3-bromobutyramide ln carrying out the process of this invention, the mol ratio of 2-amino-Z-hydrocarbylthiomethyl-l ,3- propanediol to organic halide is preferably about 1/1, however, it is within the scope of the invention that mol ratios ranging from 0.5/1 to 2/ 1 can be employed. The amino compound can be employed as the free base which can be obtained from a salt thereof e.g., as a hydrohalide or sulfate; thus, if the amine is available as the salt, it is preferably first treated with a base to liberate the free amine.

Although the reaction temperature can vary over a wide range, it would generally be within the range of about 250C., preferably within the range of about 50150C. The desired reaction time also varies over a wide range, depending in part on the reaction temperature and the nature of the reactants, but will generally be within the range of about minutes to about 5 days, preferably within the range of from 5 hours to 3 days.

In the operation of the process of this invention a solvent is not required; however, in the preferred embodiment solvents are employed. Examples of some suitable solvents include alcohols such as methanol, ethanol, n-

propyl alcohol, isopropyl alcohol, n-butyl alcohol, n-

hexyl alcohol; ethers such as ethyl ether, n-propyl ether, n-butyl ether, tetrahydrofuran, dioxane, dimethyl ether of ethylene glycol; and amides such as dimethylformamide, dimethylacetamide, and N- methylpyrrolidone.

The pressure of the reaction is preferably autogenous and need be only sufficient to maintain the reactants and their solvents substantially in a liquid phase.

As a further aspect of this invention, when R is arylmethyl or alkarylmethyl, the said N-alkylated derivative having the formula CR OH RSCR CNHR" CR OH 1 is cleaved by treatment with an alkali metal selected from the group consisting of lithium, sodium, potassium, rubidium, and cesium in the presence of ammonia to give a thiol having the formula CR OH 11 wherein R and R" are as defined hereinabove. It is noted that when R contains an arylmethyl group or an alkarylmethyl group attached to a sulfide linkage, these hydrocarbyl groups will be cleaved by an alkali metal and replaced with hydrogen.

Example of compounds of Formula 111 are as follows:

2-methylamino-Z-mercaptomethyll ,B-propanediol 2-ethylamino2-( l-mercaptobutyl)-1 ,3-propanediol 2-isopropylamino-2-( l-m ercaptoethyl)-l ,3-

propanediol 2-tert-butylamino-2-( l -mercaptol -methylpropyl)- l ,3 -propanediol 2-hexylamino-Z-mercaptomethyl- 1 ,3-but anediol 3 l ,2-diethylpentylamino)-3-mercaptomethyl-2,4-

hexanediol 2-dodecylamino-Z-mercaptomethyl- 1 ,3-hexanediol 2-cyclohexylamino-2-mercaptomethyl-1 ,3-

propanediol 2-(2-methylcyclopentylamino)-2-rnercaptomethyl-4- methyl-l ,3-pentanediol 2-( 2-cyclohexylethylamino )-2-mercaptomethyll ,3-

propanediol 2-( Z-phenylethylamino)-2-mercaptomethyll ,3-

propanediol 2-(4-methylbenzylamino)-2-( l-mercapto 'Z-m'ethylpropyl)- 1 ,3-propanediol 5-( 3-hydroxypropylamino )-5-( l-mercaptopropyl 4,6-nonanediol 2-(4-ethoxybutylamino)-2-mercaptomethyl-3-methyll ,3-butanediol 2-( 3-methylthiopropylamino )-2-mercaptomethyl- 1 ,3-propanediol 2-( 3-carboxycyclopentylamino )-2-mercaptomethyll ,3-propanediol 2-( 3-carbamoylpropylamino)-2-mercaptomethyll ,3-propanediol In this cleavage step, the amount of alkali metal actually required will vary depending upon the number of reactive groups such as hydroxy, carboxy, arylmethylthio, and alkarylmethylthio which are present, ap-

proximately 1 mol of alkali metal being required for each group such as hydroxy or carboxy containing a hydrogen atom readily replaceable by the alkali metal and approximately 1.8 mols of alkali metal being required for each arylmethylthio or alkarylmethylthio group. This amount of alkali metal is usually sufficient to impart a blue cast to the resulting solution which persists for at least 30 minutes. At least 3 mols, preferably at least 10 mols, of ammonia per mol of alkali metal is employed. The amine containing the arylmethylthio or alkarylmethylthio group can be employed as the free base or as a salt, e. g., hydrohalide or sulfate thereof. Although the reaction temperature in this cleavage step can vary over a wide range, it will generally be within the range of about to 50C., usually being approximately the normal boiling point of liquid ammonia. The desired reaction time varies over a wide range, depending in part on the reaction temperature, but will generally be within the range of about 30 minutes to about 12 hours, usually being within the range of from 1 to 6 hours. Although the ammonia conveniently serves as a solvent, an additional solvent can be used in conjunction with the ammonia if desired.

Examples of suitable additional solvents include ethers such as ethyl ether, n-propyl ether, n-butyl ether,

tetrahydrofuran, dioxane, dimethyl ether of ethylene glycol and the like. Less preferably alcohols such as methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, n-hexyl alcohol and the like can be employed.

The novel compounds produced by the process of this invention are useful as flotation agents, and those compounds which are cleaved to form the mercapto substituents are useful as intermediates in the preparation of anti-radiation drugs. These compounds are also useful as rubber modifiers and as chelating agents in the separation of metals.

It is to be understood that these compounds can be prepared in a continuous medium in the manner disclosed hereinabove and can be recovered by conventional methods, such as crystallization, distillation, solvent extraction, and the like. These recovery operations are conventional steps and are familiar to those skilled in the art. The technique for the recovery of specific compounds can vary somewhat due to differences EXAMPLE I PREPARATION OF 2-BENZY LTHIOMETHYL-2-( N-OCTYLAMINO l,3-PROPANEDIOL HYDROCHLORIDE A solution of 131.9 g (0.5 mol) of 2-amino-2 benzylthiomethyl-l,3-propanediol hydrochloride in 500 ml of ethanol was neutralized with 20 g (0.5 mol) of sodium hydroxide, and the sodium chloride was removed by filtration. The filtrate was heated at reflux temperature with 74.3 g (0.5 mol) of n-octyl chloride for 24 hours. The solution was distilled through a 45-in. Vigreux column until the pot temperature reached 120C at which point an exothermic reaction occurred and the temperature rose to 155C. After one hour, the temperature began to fall, and the reaction mixture was held at 150C. for an additional hour with external heating. Unreacted n-octyl chloride (0.124 mol) was removed by distillation. The residual oil was dissolved in 500 ml of toluene, and the solution was saturated with hydrogen chloride. The resulting semisolid was triturated with warm chloroform to give a 20 percent yield (38.5 g) of the dried product, 2- benzylthiomethyl-2-( n-octylamino l ,3-propanediol hydrochloride, m.p. 127-128C. Recrystallization from tetrahydrofuran did not change the melting point. The elemental analysis was as follows:

Element Calculated for C H NO S'HCI Found C 60.69 60.7 H 9.1 1 9.1 N 3.73 3.6

EXAMPLE II PREPARATION OF Z-MERCAPTOMETHYL-2(N-OCTYLAMINO)-1,3- PROPANEDIOL HYDROCHLORIDE A slurry of 31 g (0.03 mol) of 2-(n-octylamino)-2- benzylthiomethyl-l,3-propanediol hydrochloride in 100 ml of tetrahydrofuran was added to a liter of liquid ammonia at approximately 3 3C. and atmospheric pressure. Addition of 7 g (0.30 mol) of sodium resulted in a solution which remained blue for an hour. The solution was neutralized with 16 g (0.30 mol) of ammonium chloride. After addition of 250 ml of n-propyl alcohol, the ammonia was boiled off. The mixture was then saturated with hydrogen chloride. After warming, the inorganic salts were removed by filtration. The filtrate was stripped by dryness. The residual oil was extracted with 250 ml of ether. The viscous residue was dissolved in tetrahydrofuran, and the solutionwas saturated with hydrogen chloride; no crystallization occurred. Similar attempts to induce crystallization from methanol and n-propyl alcohol as solvents were unsuccessful. The oil was dried at 100C. in vacuo to give a 40 percent yield (9.0 g) of the 2-mercaptomethyl-2-(noctylamino)-l ,3-propanediol hydrochloride. The elemental analysis was as follows:

Element Calculated for C H,-,NO,S'HCl Found C 50.42 50.75 H 9.87 9.95 N 4.90 4.7 S l 1.22 l 1.3

EXAMPLE III PREPARATION OF 2-BENZYLTHIOMETHYL-2-( Z-HYDROXYE- THYLAMINO)-l ,S-PROPANEDIOL HYDROCHLORIDE A solution of 131.9 g (0.5 mol) of 2-amino-2- benzylthiomethyl-l,3-propanediol hydrochloride in 250 ml of methanol was neutralized with 20 g (0.5 mol) of sodium hydroxide. The sodium chloride was removed by filtration. The filtrate was heated at reflux temperature for 24 hours with 40 g (0.5 mol) of 2- chloroethanol. The solvent was removed through use of a 60-cm column packed with glass helices; at C, an exothermic reaction occurred. The dark residue was crystallized from 250 ml of tetrahydrofuran to give a 20 percent yield (31 g) of 2-benzylthiomethyl-2-(2- hydroxyethylamino)-l ,3-propanediol hydrochloride, m.p. l07108.5C. The elemental analysis was as follows:

PREPARATION OF Z-MERCAPTOMETHY L-2-( 2-HYDROXYE- THYLAMINO)-l ,3-PROPANEDIOL HYDROCHLORIDE A slurry of 31 g (0.1 mol) of 2-benzylthiomethyl-2- (2-hydroxyethyl-amino)-l ,3-propanediol hydrochloride in ml of tetrahydrofuran was added to one liter of liquid ammonia at approximately 3 3C. and atmospheric pressure. Sodium (8.5 g. 0.37 mol) was added to maintain a blue solution for 1 hour. The solution was neutralized with 20 g (0.37 mol) of ammonium chloride, and the ammonia was boiled off. A cold suspension of the residue in 150 ml of n-propyl alcohol was saturated with hydrogen chloride. The mixture was warmed, and inorganic salts were removed by filtration. The filtrate was stripped. The residue was washed with ether to give a crystalline solid. Two recrystallizations from a mixture of isopropyl alcohol and methanol gave a 31 percent yield (6.8 g) of the 2- mercaptomethyl-2-(2-hydroxyethylamino)-1 ,3- propanediol hydrochloride, m.p. lOl .5-l02C. The elemental analysis was as follows:

Element Calculated for C H,,NO;,S'HCl Found Element Calculated for C H NO S'HCl Found H 7.41 7.5 N 6.43 6.6 S 14.7 13.9 (mercaptan) EXAMPLE V PREPARATION OF 2-BENZYLTHIOMETHYL-2-( 3-PHENYL- PROPYLAMINO)- l ,3-PROPANEDIOL HYDROCHLORIDE A solution of 66 g (0.25 mol) of 2-amino-2- benzylthiomethyl-1,3-propanediol hydrochloride, in 100 ml of methanol was neutralized with g (0.25 mol) of sodium hydroxide, and the sodium chloride was removed by filtration. The filtrate was evaporated, and the free base was dissolved in ISO ml of N- methylpyrrolidone. After the addition of 39 g (0.55 mol) of l-chloro-3-phenyl-propane, the solution was heated at l40C. for 48 hours. The reaction mixture was poured into a liter of water; the oil which separated was acidified with 50 ml of concentrated hydrochloric acid. Subsequent addition of water gave a crystalline solid which was recrystallized from chloroform to give a 34 per cent yield (32 g) of the 2-benzylthiomethyl-2- (3-phenylpropylamino)-l ,3-pr0panediol hydrochloride, m.p. l2ll22C. The elemental analysis was as follows:

PREPARATION OF 2-MERCAPTOMETHYL-2-( 3-PHENYL- PROPYLAMINO)- 1 ,3-PROPANEDIOL HYDROCHLORIDE A slurry of 32 g (0.08 mol) of 2-benzylthiomethyl-2- (3-phenylpropylamino )-l ,3-propanediol hydrochloride in 100 ml of tetrahydrofuran was added to one liter of liquid ammonia at approximately -33C. and atmospheric pressure. Sodium (8 g, 0.33 mol) was added to the resulting mixture to maintain a blue color for one hour. The mixture was neutralized with 18 g (0.34 mol) of ammonium chloride, and the ammonia was boiled off. A cold slurry of the residue in 200 ml of n-propyl alcohol was saturated with hydrogen chloride. After warming, the inorganic salts were removed by filtration. The filtrate was stripped, .and the residual oil was extracted three times with ether. Drying the residue in vacuo gave 2-mercaptomethyl-2-(3-phenylpropylamino)-l ,3-propanediol hydrochloride as a clear glass. The elemental analysis was as follows:

Element Calculated for C,,H,,NO,S'HCI Found C 53.55 52.4 H 7.59 8.4 N 4.79 4.04 S 10.98 9.0

8 EXAMPLE vn PREPARATION OF 2-BENZYLTHIOMETHYL-2-(Z-CARBAMOYLE- THYLAMINO)-l ,3-PROPANEDIOL HYDROCHLORIDE A solution of 132 g 1 (0.50 mol) of 2-amino-2- benzylthiomethyl-l,3-propanediol hydrochloride in 500 ml of tetrahydrofuran was neutralized with 20 g (0.50 mol) of sodium hydroxide, and the sodium chloride was removed by filtration. To the filtrate was added 53.8 g (0.50 mol) of 3-chloropropionamide, and the solution was heated at reflux temperature for 24 hours. The solvent was removed, and the reaction mixture was heated 48 hours on a steam bath. The product was dissolved in 300 ml of tetrahydrofuran and ml of acetonitrile; cooling at l0C. gave 79 g of crude product, m.p. ll9-121C. Recrystallization from tetrahydrofuran gave a 27 percent yield (46 g) of the 2- benzylthiomethyl-2-( 2-carbamoylethylamino 1 ,3 propanediol hydrochloride, m.p. l45-l47C. The elemental analysis was as follows:

Element Calculated for C H N O SHCI Found C 50.21 49.8 H 6.92 7.3 N 8.37 8.7

EXAMPLE VIII A slurry of 46 g (0.137 mol) of Z-benzylthiomethyl- 2-( 2-carbamoylethylamino l ,3-propanediol hydrochloride in 200 in] of tetrahydrofuran was added to one liter of liquid ammonia at approximately 33C. and atmospheric pressure; to the mixture was added 15.8 g (0.6 mol) of sodium to maintain a blue color for one hour. The mixture was neutralized with 33 g (0.6 mol) of ammonium chloride, and the ammonia was boiled off. The product was suspended in 250 ml of cold npropyl alcohol, and the mixture was saturated with hydrogen chloride. After warming, the inorganic salts were removed by filtration. The filtrate was evaporated to yield a semisolid. The latter was extracted with 200 ml of ether and then with 200 ml of boiling tetrahydrofuran to remove bi-benzyl. The water-white viscous oil resisted attempts at crystallization from various solvent combinations. Portionwise addition of ether to a solution in N-propyl alcohol gave three fractions (all viscous oils) 2.9 g, 5.3 g, and 11.7 g, which were vacuumdried for 24 hours at 65C. The intermediate fraction which was substantially pure 2-mercaptomethyl-2-(2- carbamoylethylamino)- l ,3-propanediol hydrochloride was subjected to elemental analysis. The elemental analysis was as follows:

Element Calculated for C-,I-I, N O S-l-ICl Found c 34.34 35.75 H 7.00 7.25 N 11 .45 9.; s 1 3. 10 10.9

Gas chromatographic analysis of the sample showed the following impurities (in weight percent): Ether, 0.1; tetrahydrofuran, 2.8; n-propyl alcohol, 0.2.

EXAMPLE 1x PREPARATION OF (2-CHLOROETHYL)CYCLOHEXANE Element Calculated for C H CI Found EXAMPLE X PREPARATION OF Z-BENZY LTHIOM ETHYL-2-( Z-CYCLOHEXY LE- THYLAMlNO)-l ,3-PROPANEDIOL HYDROCHLORIDE A solution of 174 g (0.66 mol) of 2-amino-2- benzylthiomethyl-l,3-propanediol hydrochloride in 250 ml of methanol was neutralized with 26.4 g (0.66 mol) of sodium hydroxide, and the sodium chloride was removed by filtration. The solvent was stripped off. To the resulting free base was added 96 g (0.66 mol) of (2-chloroethyl)cyclohexane in 250 ml of tetrahydrofuran. The reaction mixture was heated at reflux temperature for 16 hours. The solvent was distilled, and the residue was heated at 140C. for 16 hours. The crystalline product was recrystallized twice from 300 ml of acetonitrile to give a 36 percent yield (90 g) of the 2- benzylthiomethyl-2-( 2-cyclohexylethylamino)-l ,3- propanediol hydrochloride, m.p. l49151C. The elemental analysis was as follows:

PREPARATION OF 2-MERCAPTOMETHYL-2-( Z-CYCLOHEXYLE- THYLAMlNO)-l ,3-PROPANEDIOL HYDROCHLORIDE A slurry of 90 g (0.24 mol) of 2-benzylthiomethyl-2- I (2-cyclohexylethylamino)-1,3-propanediol hydrochloride in 250 ml of tetrahydrofuran was added to one liter of liquid ammonia at approximately -33C. and atmospheric pressure. The slurry was treated with 20 g (0.87 mol) of sodium metal to maintain a blue color for one hour. The mixture was neutralized with 50 g (0.93 mol) of ammonium chloride, and the ammonia was evaporated. A cold mixture of the residue in 250 ml of npropyl alcohol was saturated with hydrogen chloride. The mixture was warmed, and the inorganic salts were removed by filtration. The filtrate was evaporated, and

the residue was extracted twice with ether. The residue was recrystallized once from a mixture of tetrahydrofuran and ether and once from a mixture of acetonitrile and tetrahydrofuran to give a 44 percent yield (30 g) of the 2-mercaptomethyl-2-(2-cyclohexylethylamino)- 1,3-propanediol hydrochloride, m.p. 123-125C. The elemental analysis was as follows:

Element Calculated for c,.H,,N0,s-HCl Found C 50.77 50.5 H 9.23 9.3 N 4.93 5.25 S l 1.30 10.5 (mercaptan) EXAMPLE XII PREPARATION OF 2-BENZYLTHIOMETHYL-2-( 3-HYDROXY- PROPYLAMlNO)-l ,3-PROPANEDIOL HYDROCHLORIDE A solution of 113.5 g (0.5 mol) of 2-amino-2- benzylthiomethyl-l,3-propanediol, 47.3 g (0.5 mol) of v Element Calculated for C H NO,,S'HCl Found C 52.24 51.1 H 7.52 7.7 N 4.35 4.4 S 9.96 9.3

EXAMPLE XIII PREPARATION OF 2-BENZYLTHIOMETHYL-2-( 2-BENZYLTHIOE- THYLAMINO)-l ,3-PROPANEDIOL HYDROCHLORIDE A mixture of 62 g (0.33 mol) of benzyl 2-chloroethyl sulfide, g (0.33 mol) of 2-amino-2-benzylthiomethyl-l,3-propanediol, 36 g (0.33 mol) of sodium carbonate, and 300 ml of xylene was stirred vigorously under reflux for eight hours. After cooling, the mixture was diluted with an equal volume of ether and washed several times with water. The organic layer was evaporated under aspirator pressure. The residual oil was mixed with 500 ml of isopropyl alcohol and ml of concentrated hydrochloric acid. After evaporation of the resulting solution, the residual oil was dissolved in acetonitrile. Cooling gave the 2-benzylthiomethyl-2- Element Calculated for C H NO S HCI Found C 58.03 57.8 H 6.82 6.8 N 3.38 3.65

EXAMPLE XIV PREPARATION OF 2-MERCAPTOMETHYL-2-( MERCAPTOE- Tl-lYLAMlNO)-l ,B-PROPANEDIOL HYDROCHLORIDE A solution of 2-benzylthiomethyl-2-(2-benzylthioethylamino)-l,3-propanediol hydrochloride (74 g, 0.18 mol) was prepared in 1 liter of liquid ammonia at approximately 3 3C. and atmospheric pressure. Sodium (24 g, 1 mol) was added in small pieces to maintain a blue color for two hours. The solution was neutralized with 20 g of ammonium chloride. All subsequent operations were carried out under nitrogen. After evaporation of the ammonia, 500 ml of tetrahydrofuran and 250 ml of 95 percent ethanol were added to the residue. The mixture was heated to 40C; after cooling to C., the mixture was filtered. The solid was washed twice with isopropyl alcohol. The combined solutions were evaporated to dryness under aspirator pressure; the residual oil rapidly solidified. It was taken up in 400 ml of hot isopropyl alcohol, and a slight turbidity was removed by filtration. The filtrate was saturated with hydrogen chloride. An inorganic solid separated and was removed. Evaporation and dissolution of the residue in isopropyl alcohol gave more inorganic material, as did cooling the solution to -70C. Finally addition of ether to the alcohol solution gave, at 70C., a crystalline solid that became an oil at room temperature. It was filtered on a funnel cooled with circulating acetone chilled at 60C. drying in a high vacuum overnight did not remove completely occluded or solvated isopropyl alcohol, found upon gas chromatographic analysis. The elemental analysis was as follows:

It is to be understood that although in the preceding examples all the novel compounds were permitted to remain as the salts thereof, that it is within the skill of a chemist to free these novel compounds from the salt by merely treating them with a suitable base such as sodium or potassium hydroxide.

Obviously many modifications and variations of the present invention are possible in the light of the above teachings. It is therefore to be understood that within the scope of the appending claims the invention may be practiced otherwise than as specifically described here- We claim:

l. A compound selected from the group consisting of compounds having the formula:

CRgOH RSCR CNHR" CR OH wherein each R is hydrogen or an alkyl radical containing 1-3 carbon atoms; R is hydrogen or an alkyl, cycloalkyl, or aryl radical or combination thereof containing 1-12 carbon atoms; R" is a carboxy-substituted hydrocarbyl radical, said hydrocarbyl radical being an alkyl, cycloalkyl, or aralkyl radical or combination thereof, R" containing up to 12 carbon atoms; and wherein the total number of carbon atoms in said compound is within the range of 6-36.

2. A compound selected from the group consisting of compounds having the formula:

wherein R and R are as defined in claim 8, and wherein the total number of carbon atoms in said compound is within the range of 6-36.

3. A compound in accordance with claim 1 wherein R is hydrogen or an alkyl radical containing 1 to 12 carbon atoms; and R is a carboxy-substituted alkyl radical containing up to 12 carbon atoms.

4. A compound in accordance with claim 1 wherein R is hydrogen or an alkyl radical containing 1 to 12 carbon atoms; and R is a carboxy-substituted cycloalkyl radical containing up to 12 carbon atoms.

5. A compound in accordance with claim 1 wherein R is hydrogen or an alkyl radical containing 1 to 12 carbon atoms; and R is a carboxy-substituted aralkyl radical containing up to 12 carbon atoms.

6. A compound in accordance with claim 1 wherein R is hydrogen or a cycloalkyl radical containing 1 to 12 carbon atoms; and R is a carboxy-substituted alkyl radical containing up to 12 carbon atoms.

7. A compound in accordance with claim 1 wherein R is hydrogen or a cycloalkyl radical containing 1 to 12 carbon atoms; and R" is a carboxy-substituted cycloalkyl radical containing up to 12 carbon atoms.

8. A compound in accordance with claim 1 wherein R is hydrogen or a cycloalkyl radical containing 1 to 12 carbon atoms; and R is a carboxy-substituted aralkyl radical containing up to 12 carbon atoms.

9. A compound in accordance with claim 1 wherein R is hydrogen or an aralkyl radical containing 1 to 12 carbon atoms; and R is a carboxy-substituted alkyl radical containing up to 12 carbon atoms.

10. A compound in accordance with claim 1 wherein R is hydrogen or an aralkyl radical containing 1 to 12 carbon atoms; and R is a carboxy-substituted cycloalkyl radical containing up to 12 carbon atoms.

11. A compound in accordance with claim 1 wherein R is hydrogen or an aralkyl radical containing 1 to 12 carbon atoms; and R is a carboxy-substituted aralkyl radical containing up to 12 carbon atoms.

of claim 1.

2-( 3-carboxycyclopentylamino)-2-mercap- UNITED STATES PATENT AND TRADEMARK OFFICE QERHHQATE 0F GRREUHN PATENT NO. I 3,789,069

DATED I January 29, 1974 INVENTOMS) 1 Clarence R. Bresson; Raymond L. Cobb It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 12, line 24, delete "8" and insert l Signed and Scaled this twenty-seventh D3) of April 1976 [SEAL] A rtest:

RUTH c. MASON c. MARSHALL DANN Arresting Officer (mnmissimn'r uj'Parenrs and Trademarks 

2. A compound selected from the group consisting of compounds having the formula:
 3. A compound in accordance with claim 1 wherein R'' is hydrogen or an alkyl radical containing 1 to 12 carbon atoms; and R'''' is a carboxy-substituted alkyl radical containing up to 12 carbon atoms.
 4. A compound in accordance with claim 1 wherein R'' is hydrogen or an alkyl radical containing 1 to 12 carbon atoms; and R'''' is a carboxy-substituted cycloalkyl radical containing up to 12 carbon atoms.
 5. A compound in accordance with claim 1 wherein R'' is hydrogen or an alkyl radical containing 1 to 12 carbon atoms; and R'''' is a carboxy-substituted aralkyl radical containing up to 12 carbon atoms.
 6. A compound in accordance with claim 1 wherein R'' is hydrogen or a cycloalkyl radical containing 1 to 12 carbon atoms; and R'''' is a carboxy-substituted alkyl radical containing up to 12 carbon atoms.
 7. A compound in accordance with claim 1 wherein R'' is hydrogen or a cycloalkyl radical containing 1 to 12 carbon atoms; and R'''' is a carboxy-substituted cycloalkyl radical containing up to 12 carbon atoms.
 8. A compound in accordance with claim 1 wherein R'' is hydrogen or a cycloalkyl radical containing 1 TO 12 carbon atoms; and R'''' is a carboxy-substituted aralkyl radical containing up to 12 carbon atoms.
 9. A compound in accordance with claim 1 wherein R'' is hydrogen or an aralkyl radical containing 1 to 12 carbon atoms; and R'''' is a carboxy-substituted alkyl radical containing up to 12 carbon atoms.
 10. A compound in accordance with claim 1 wherein R'' is hydrogen or an aralkyl radical containing 1 to 12 carbon atoms; and R'''' is a carboxy-substituted cycloalkyl radical containing up to 12 carbon atoms.
 11. A compound in accordance with claim 1 wherein R'' is hydrogen or an aralkyl radical containing 1 to 12 carbon atoms; and R'''' is a carboxy-substituted aralkyl radical containing up to 12 carbon atoms.
 12. 2-(3-carboxycyclopentylamino)-2-butylthiomethyl-1-3 propanediol, the product of the formula of claim
 1. 13. 2-(3-carboxycyclopentylamino)-2-mercaptomethyl-1, 3-propanediol, the product of the formula of claim
 1. 